Introduction

Uses for Femara

Breast Cancer

Adjuvant treatment in postmenopausal women with early-stage hormone receptor-positive breast cancer.1394041 Superior to tamoxifen when each drug was given alone;14052 efficacy of sequential therapy (tamoxifen for 2 years followed by letrozole for 3 years, or vice versa) similar to that of letrozole given for 5 years.3952

Extended adjuvant treatment in postmenopausal women with early-stage breast cancer who have received 5 years of adjuvant tamoxifen therapy.19253841

Aromatase inhibitors are a treatment of choice for adjuvant hormonal therapy to lower risk of breast cancer recurrence in postmenopausal women with early-stage hormone receptor-positive breast cancer.941 An aromatase inhibitor-containing regimen is modestly more effective than tamoxifen alone.941

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ASCO states that most postmenopausal women with early-stage hormone receptor-positive breast cancer should consider receiving an aromatase inhibitor during the course of adjuvant therapy, either as primary (initial) therapy or following 2–3 years of tamoxifen (sequential therapy), for a total of 5 years of adjuvant endocrine therapy.41 Data also support switching to an aromatase inhibitor following 5 years of adjuvant tamoxifen (extended adjuvant therapy).41 ASCO states that women who receive extended adjuvant therapy should receive tamoxifen for 5 years followed by an aromatase inhibitor for 3–5 years.41

In combination with lapatinib for treatment of hormone receptor-positive metastatic breast cancer that overexpresses the human epidermal receptor type 2 (HER2) protein in postmenopausal women who are candidates for hormonal therapy.444953 Combined therapy with an aromatase inhibitor and lapatinib has not been compared with trastuzumab-containing chemotherapy for treatment of metastatic breast cancer.49

Female Infertility

Has been used to induce ovulation† in anovulatory women desiring pregnancy.d Letrozole is not FDA-labeled for this indication;e manufacturer states that the drug is contraindicated in women who may become or are pregnant.1 (See Fetal/Neonatal Morbidity and Mortality under Cautions.)

Sequential adjuvant therapy: Optimal time to switch from tamoxifen to aromatase inhibitor therapy is unknown.41 ASCO states that disease-free patients may switch to an aromatase inhibitor after 2–3 years of adjuvant tamoxifen therapy to complete a 5-year sequential adjuvant regimen.41

Extended adjuvant therapy: Initiate letrozole after completion of 5 years of adjuvant tamoxifen therapy.12541 Planned duration of letrozole treatment in clinical study was 5 years;125 71% of patients completed ≥3 years and 58% completed ≥4.5 years of treatment.1 ASCO recommends administering an aromatase inhibitor for 3–5 years beyond the initial 5 years of tamoxifen therapy, for a total of 8–10 years of adjuvant endocrine therapy.41 Optimal duration unknown.125

Cautions for Femara

Contraindications

Warnings/Precautions

Fetal/Neonatal Morbidity and Mortality

May cause fetal harm.1 Embryotoxic, fetotoxic, and teratogenic in animals.1 Contraindicated in women who are or may become pregnant (i.e., premenopausal women).1 If inadvertently used during pregnancy or patient becomes pregnant, apprise of fetal hazard.1 Women who are perimenopausal or recently have become postmenopausal should use adequate contraception until postmenopausal state is fully established.1

Effects on Bone

Postmenopausal women receiving an aromatase inhibitor as adjuvant therapy are at high risk for osteoporosis.29

Bone mineral density (BMD) at lumbar spine decreased by 4.1% over 2 years in patients receiving adjuvant letrozole and increased by 0.3% in those receiving tamoxifen; results for hip BMD were similar, but difference was less pronounced.1 Incidence of osteoporosis (5 versus 3%) and fractures (14 versus 10%) was higher during or after treatment with letrozole versus tamoxifen.1

Hip BMD decreased by 4 or 2% over 2 years in patients receiving extended adjuvant therapy with letrozole or placebo, respectively.1 Incidence of osteoporosis (14 versus 8%) and fracture (13 versus 8%) was higher during or after treatment with letrozole versus placebo.1

Lactation

Pediatric Use

Geriatric Use

Initial adjuvant therapy: 36% of study patients were ≥65 years of age and 12% were ≥75 years of age.1 Adverse effects generally more common in geriatric patients regardless of their assigned study treatment; however, no overall differences in safety and efficacy of letrozole versus tamoxifen were observed between geriatric patients and younger adults.1

Extended adjuvant therapy: 41% of study patients were ≥65 years of age and 12% were ≥75 years of age.1 No substantial differences in safety and efficacy relative to younger adults, but increased sensitivity cannot be ruled out.1

First- and second-line treatment: Median patient age in all studies was 64–65 years; one-third were ≥70 years of age.1 In the first-line clinical study, patients ≥70 years of age experienced longer time to tumor progression and higher response rates than patients <70 years of age.1

Premenopausal Women

Clinical benefit not established in premenopausal women with breast cancer.1 Contraindicated in premenopausal women.1

Elimination Route

Half-life

Special Populations

Renal function did not affect the pharmacokinetics of a single 2.5-mg dose in adults with varying renal function.1 Renal impairment (Clcr 20–50 mL/minute) did not affect steady-state plasma concentrations in patients with advanced breast cancer.1

Risk of fetal harm if used during pregnancy.1 Necessity for perimenopausal or recently postmenopausal women to use adequate contraception until postmenopausal state is fully established.1 Contraindicated in premenopausal women.1

Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.1

Importance of informing patients of other important precautionary information.1 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Letrozole

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets, film-coated

2.5 mg

Femara

Novartis

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2015. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

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